The Genetic Study of Families with a High Frequency of Hematopoietic Malignancy

条款摘要 霍奇金淋巴瘤（HL）和B前体急性淋巴细胞白血病（B-ALL）是常见的 儿童恶性肿瘤，有家族聚集的证据。这个家庭 聚集可以用DNA的变化来解释，DNA的变化可能导致疾病， 代代相传然而，到目前为止，关于哪些突变在 在家族中，基因导致HL或B-ALL。为了更好地识别这些基因，我们 进行了全基因组测序（WGS）的最大的一组家庭与高 HL或B-ALL的频率。从受影响的和未受影响的两个方面获取此WGS信息 家庭成员提高了找到这些重要的潜在遗传基础的可能性。 家庭中的儿童癌症。对我们的WGS结果的初步分析表明， 确定了潜在的感兴趣的基因，但需要广泛的分析来询问编码 区域、非编码区、拷贝数变体和结构变体。我们的所有调查结果 然后将在这些疾病患者的零星队列中验证家庭的频率 已经进行了WGS，其数据可用于分析。本研究 重要的是，它提供了一种创新和全面的方法来回答 是什么使患者易患HL和B-ALL的问题。知识 通过这项研究获得的信息将是无价的，因为它将帮助我们了解这种疾病的起源。 为HL和B-ALL患者确定更好的筛查、预防和治疗。

Lay Summary Hodgkin Lymphoma (HL) and B precursor acute lymphoblastic leukemia (B-ALL) are common malignancies of childhood with well documented evidence of familial clustering. This familial clustering may be explained by changes in DNA which may lead to diseases that can be passed from generation to generation. However, to date little is known regarding which mutations in genes are causing HL or B-ALL within families. To better identify these genes, we have performed whole genome sequencing (WGS) on the largest group of families with a high frequency of HL or B-ALL. Having this WGS information from both affected and unaffected family members improves the possibility of finding a potential genetic basis of these important pediatric cancers of childhood within the families. Preliminary analyses of our WGS results have identified potential genes of interest, but extensive analysis is needed to interrogate coding regions, non-coding regions, copy number variants and structural variants. All findings from our families will then be validated for frequency in a sporadic cohort of patients with these diseases that have already have WGS performed and their data are available for analyses. This research is important because it provides an innovative and comprehensive approach to answering the question of what predisposes patients to the development of HL and B-ALL. The knowledge gained through this study will be invaluable as it will help us understand the origin of the disease and identify better screening, prevention and treatment for patients with HL and B-ALL.